Aqueous solubility of poorly water-soluble drugs: Prediction using similarity and quantitative structure-property relationship models

Junhyoung Kim; Dong Hyun Jung; Hokyoung Rhee; Seung-Hoon Choi; Min Jae Sung; Woo Sik Choi

Korean Journal of Chemical Engineering, Vol.25, No.4, 865-873, July, 2008

DOI10.1007/s11814-008-0143-x Export Citation

Aqueous solubility of poorly water-soluble drugs: Prediction using similarity and quantitative structure-property relationship models

Junhyoung Kim¹, Dong Hyun Jung¹, Hokyoung Rhee¹, Seung-Hoon Choi¹, Min Jae Sung², and Woo Sik Choi^{2, 3, †}

¹Insilicotech Co. Ltd., A-1101 Kolontripolis, 210, Geumgok-dong, Bundang-gu, Seongnam-shi 463-943, Korea
²Interdisciplinary Program in Powder Technology, Graduate School, Pusan National University, 30, Jangjeon-dong, Geumjeong-gu, Busan 609-735, Korea
³Department of Pharmaceutical Manufacturing, Pusan National University, 30, Jangjeon-dong, Geumjeong-gu, Busan 609-735, Korea

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The aqueous solubility of poorly water-soluble drugs is an important property of many factors affecting their bioavailability such as the solubility and rate of dissolution in water. The quantitative structure-property relationship approach using genetic algorithm was applied to make models for predicting some poorly water-soluble drugs such as ursodeoxycholic acid, diphenyl hydrantoin and biphenyl dimethyl dicarboxylate. The experimental solubility data of 3518 chemical structures were collected from the web and used to build a model. Three data sets of 50 compounds were extracted according to their structural similarity with each drug. A fast and predictive similarity based approach was developed and validated with conventional method. This can be used to predict the aqueous solubility for drugs by using a small set of compounds, especially for poorly water-soluble compounds. Moreover, the estimation values of various sets were further compared with fine grinding experiment data.

Keywords:Insoluble Drug;Fine Grinding;Solubility;QSPR;UDCA;Phenytoin;DDB

[References]

Sung MJ, Cha BJ, Choi WS, Kim JH, Choi SH, The 43rd symposium on powder science and technology, Busan, Korea (2005)
Kim J, Jung DH, Rhee H, Choi SH, Sung MJ, Choi WS, Korean J. Chem. Eng., 25(1), 171 (2008)
Lipinski CA, Lombardo F, Dominy BW, Feeney PJ, Adv. Drug Deliv. Rev., 23, 3 (1997)
Dearden JC, Chemom. Intell. Lab. Syst., 24, 77 (1994)
Jorgensen WL, Duffy EM, Adv. Drug Deliv. Rev., 54, 355 (2002)
Taskinen J, Yliruusi J, Adv. Drug Deliv. Rev., 55, 1163 (2003)
Cramer RD, J. Med. Chem., 46, 374 (2003)
ChemIDplus, http://chem.sis.nlm.nih.gov/chemidplus/
PubChem, http://pubchem.ncbi.nlm.nih.gov/
Cerius2., Accelrys, San Diego, CA
Hall LH, Kier LB, J. Chem. Inf. Comput. Sci., 35, 1039 (1995)
Devillers J, Genetic algorithms in molecular modeling, Academic Press, San Diego (1996)
Mitchel BE, Jurs PC, J. Chem. Inf. Comput. Sci., 38, 489 (1998)
Stanton DT, Jurs PC, Anal. Chem., 62, 2323 (1990)
Rohrbaugh RH, Jurs PC, Anal. Chim. Acta, 199, 99 (1987)
Arlt W, Private communication on the prediction of thermo-physical data, University of Erlangen, Germany (2005)

[Referenced By]

[1] Sung MJ, Cha BJ, Choi WS, Kim JH, Choi SH, The 43rd symposium on powder science and technology, Busan, Korea (2005)

[2] Kim J, Jung DH, Rhee H, Choi SH, Sung MJ, Choi WS, Korean J. Chem. Eng., 25(1), 171 (2008)

[3] Lipinski CA, Lombardo F, Dominy BW, Feeney PJ, Adv. Drug Deliv. Rev., 23, 3 (1997)

[4] Dearden JC, Chemom. Intell. Lab. Syst., 24, 77 (1994)

[5] Jorgensen WL, Duffy EM, Adv. Drug Deliv. Rev., 54, 355 (2002)

[6] Taskinen J, Yliruusi J, Adv. Drug Deliv. Rev., 55, 1163 (2003)

[7] Cramer RD, J. Med. Chem., 46, 374 (2003)

[8] ChemIDplus, http://chem.sis.nlm.nih.gov/chemidplus/

[9] PubChem, http://pubchem.ncbi.nlm.nih.gov/

[10] Cerius2., Accelrys, San Diego, CA

[11] Hall LH, Kier LB, J. Chem. Inf. Comput. Sci., 35, 1039 (1995)

[12] Devillers J, Genetic algorithms in molecular modeling, Academic Press, San Diego (1996)

[13] Mitchel BE, Jurs PC, J. Chem. Inf. Comput. Sci., 38, 489 (1998)

[14] Stanton DT, Jurs PC, Anal. Chem., 62, 2323 (1990)

[15] Rohrbaugh RH, Jurs PC, Anal. Chim. Acta, 199, 99 (1987)

[16] Arlt W, Private communication on the prediction of thermo-physical data, University of Erlangen, Germany (2005)